Light-screening compositions and method

ABSTRACT

Oral compositions for the treatment of erythema caused by the sun utilizing as the active ingredient canthaxanthin in combination with other carotenoids are disclosed.

United States Patent [191 Kl'ziui et a1.

[ Nov. 18, 1975 LIGHT-SCREENING COMPOSITIONS AND METHOD [75] Inventors:Heinrich Kliiui, Riehen; Wilheim Friedrich Kiir'ner, Bettingen, both ofSwitzerland [73] Assignee: Hoffmann-La Roche Inc., Nutley,

[22] Filed: Sept. 11, 1973 [21] Appl. No.: 396,278

Related US. Application Data [63] Continuation-in-part of Ser. No.153,118, June 14,

1971, abandoned.

[30] Foreign Application Priority Data July 10, 1970 Switzerland10481/70 [56] References Cited UNITED STATES PATENTS 3,252,864 5/1966Klaui 424/331 3,252,865 5/1966 Klaui 424/331 FOREIGN PATENTS ORAPPLICATIONS 2,129,653 1/1972 Germany OTHER PUBLICATIONS British Journalof Dermatology, Vol. 77, Dec. 1965, pp. 622-626.

J. of Invest. Derm, Vol. 32, Jan-June 1959, pp,

Chemical Abstracts, Vol. 65:10423b, Referring to Belg. Patent 670,243and Vol. 63:1106g to egg yolk.

Primary Examiner-Donald B. Meyer J Attorney, Agent, or FirmSamuel L.Welt; Jon S. Saxe; Gerald S. Rosen [57] ABSTRACT Oral compositions forthe treatment of erythema caused by the sun utilizing as the activeingredient canthaxanthin in combination with other carotenoids aredisclosed.

5 Claims, No Drawings I LIGHT-SCREENING COMPOSITIONS AND METHOD RELATEDAPPLICATIONS This application is a continuation-in-part of US. patentapplication Ser. No. 153,118, filed June 14, 1971 now abandoned, thebenefit of the priority date of which is hereby claimed.

BACKGROUND or THE INVENTION Prolonged exposure to the sun, particularlyin lightskinned persons, generally leads to an initial redness of theskin which becomes brown after a period of time. This redness isgenerally painful and can result in the skin peeling. The damage to theskin is caused by the ultraviolet portion of sunlight in the range ofabout 290-310 nm. Many attempts have been made to filter ofi thedamaging ultraviolet wave lengths from the skin with externally appliedsun screen agents. These. sun screen agents are generally satisfactorywhile. they are on the skin. They are glisadvantageoussince they do notremain on the skin for a sufficiently'long time to be adequatelyeffective and as a consequence have to be repeatedly reapplied atfrequent intervals. Furthermore, many of the external sun screen agentsare rather greasy and uncomfortable to the user.

There is thus a need for an effective sun screen agen which isefficacious upon prolonged use and which is facily administered.

DETAILED DESCRIPTION OF THE INVENTION It has been found according tothis invention that a sun screen agent as hereinafter defined can beadministered internally and can be stored in sufficient amounts in theskin to bring about an effect similar to the filtering effect ofconventional externally applied sun screen agents. According to thisinvention, it has been found that the internal administration ofcanthaxanthin in combination with other carotenoids has the desiredeffect. It has been found that when canthaxanthin is administered orallyin combination with other carotenoids, it, as well as the othercarotenoids, will become stored in the skin and prophylactically protectagainst sun erythema and sunburn and reduce photosenitivity.

While the use of canthaxanthin alone protects against sunburn, sunerythema and reduces photosensitivity, it imparts an undesirable reddishcolor to the skin, it can, however, be used successfully in combinationwith other carotenoids which are capable of being stored in the skin andwhich filter ultraviolet light rays in the 290-310 nm. range. Amongthose carotenoids which are suitable for use in oral sun screencompositions in combination with canthaxanthin are B-carotene, B-apo-8'-carotenal, B-apo-8'-carotenoic acid ethyl ester, bixin,zeaxanthin, crocetin, echinenone, citranaxanthin, torularhodin aldehyde,apo-4--,B-carotenal, C dialdehyde, lycopene, capsanthin, rhodoxanthinand astaxanthin.

The most preferred compounds of the above group for combination withcanthaxanthin in sun screen compositions according to this invention,are B-carotene, ,B-apo-8'-carotenal and B-apo-8-carotenoic acid ethylester. Of the remaining carotenoids which are suitable, bixin,zeaxanthin and crocetin are preferred.

The compositions containing the active ingredients are administeredinternally in any convenient dosage 2 form, preferably in the form ofcapsules. The oral ad-. ministration forms which are suitable, e.g.,capsules, can contain various amounts of active ingredients, however, atotal amount of from about 5 mg. to about 50 mg. of active ingredients,are generally used.

Preferably, however, the oral unit dosage form contains from about 10mg. to about 30 mg. of active ingreclients. The active ingredients aregenerally administered orally on a daily basis. The daily dosage amountsare usually from about 5 mg. to about 100 mg. of active ingredientsadministered in one or more doses throughout the day. It ispreferable toadminister about 50 mg. to about 100 mg. and particularly about mg. ofactive ingredients daily. The dosages and dosage regimen describedrelate to adults. The dosage for children is generally about one-halfthe dosage for adults administered in a similar daily regimen.

In order to insure the prophylactic effect against sun erythema, sunburnand reduction of photosensitivity is effected and in order to insurethat sufficient active ingredients have been stored in the tissues ofthe skin, it is necessary to treat the patient in the manner describedcontinuously during the period of about 10 to 20 days before expectedexposure to the sun. Tests on light skinned persons conducted accordingto. the method of Wucherpfennig [Strahlentherapie Vol. 40, page 201(1931)] have shown that the prophylactic use of the sun screencompositions of this invention produce a significant protective effectagainst ultraviolet rays and particularly protect against and delay theformation of erythema caused by the ultraviolet rays. Finally,prophylactic administration of the compositions of this invention topersons who are in general strong risks for sunburn, such as thoseexposed to strong sunlight in high elevations or on lakes, indicates thetreatment is successful since such persons exhibited no sun erythema orsunburn.

When the combination preparations of canthaxanthin and one or more ofthe carotenoids listed are used, then the active combination shouldpreferably contain at least about 50% by weight of canthaxanthin withthe upper limit restricted only by the reddish color imparted to theskin. Preferably up to about 75 canthaxanthin is used in thecombination. The remainder of the active combination in the oral dosageform, e.g., from about 25 to 50 by weight is a carotenoid or mixturesthereof as listed above. The oral compositions can be made byconventional compounding procedures known in the pharmaceutical art,that is, by mixing the active substances with edible pharmaceuticallyacceptable non-toxic inert, solid or liquid carriers and/or excipientssuitable for systemic administration and conventionally used in oraldosage forms. Additionally, edible, non-toxic pharmaceuticallyacceptable stabilizers such as the tocopherol compounds usually used asstabilizers in oral dosage forms or edible, non-toxic pharmaceuticallyacceptable salts thereof as well as ascorbic acid can be included in thecompositions. All the above carriers, excipients and stabilizers areintended to include only those suitable for oral administration and allare conventional and known to the pharmaceutical compounding art.

In the following examples which illustrate the invention the expression10%; water-soluble signifies water-soluble preparations which contain10% by weight of the corresponding carotenoid.

EXAMPLE 1 Capsules of the following composition are manufactured in aconventional manner:

Cunthuxanthin water-soluble) 100 mg. B-curotene I071; watersoluhle) 100mg. Mannitol 60 mg. Talcum 8 mg.

EXAMPLE 2 Capsules of the following composition are manufactured in aconventional manner:

Canthaxanthin (10%; water-soluble) 100 mg. B-carotene (10%:water-soluble) 100 mg. DL-a-Tocopheryl acetate 20 mg. Ascorbic acid 40mg. Mannitol 90 mg. Talcum 12 mg.

In the compositions prepared according to this example, equal weights ofeither B-apo-8-carotenal, B-apo- 8-carotenoic acid ethyl ester orcitranaxanthin can be used in the place of ,B-carotene.

We claim:

1. A method for the prophylactic treatment of sun erythema, sunburn andphotosensiti'vity caused by ultraviolet light rays which comprisesorally administering to a person in need of such treatment an oralcomposition comprising a. pharmaceutically acceptable carriers andexcipients or mixtures thereof, and

b. from about 5 mg. to about 50 mg. of a mixture containing from about50% to by weight of canthaxanthin and from about 25% to 50% by weight ofa carotenoid selected from the group consisting of ,B-carotene,B-apo-8'-carotenal, B-apo-8+ carotenoic acid ethyl ester, bixin,zeaxanthin, crocetin and citranaxanthin, for a period of from about 10to about 20 days prior to expected exposure to sunlight.

2. The method of claim 1 wherein component (b) is a mixture containingcanthaxanthin and B-carotene.

3. The method of claim 1 wherein component (b) is a mixture containingcanthaxanthin and B-apo-8'- carotenal.

4. The method of claim 1 wherein component (b) is a mixture containingcanthaxanthin and B-apo-8'- carotenoic acid ethyl ester.

5. The method of claim 1 wherein component (b) is a mixture containingcanthaxanthin and citranaxanthin.

1. A METHOD FOR THE PROPHYLACTIC TREATMENT OF SUN ERYTHEMA, SUNBURN ANDPHOTOSENSITIVITY CAUSED BY ULTRAVIOLET LIGHT RAYS WHICH COMPRISES ORALLYADMINISTERING TO A PERSON IN NEED OF SUCH TREATMENT AN ORAL COMPOSITIONCOMPRISING A. PHARMACEUTICALLY ACCEPTABLE CARRIERS AND EXCIPIENTS ORMIXTURES THEREOF, AND B. FROM ABOUT 5 MG. TO ABOUT 50MG. OF A MIXTURECONTAINING FROM ABOUT 50% TO 75% BY WEIGHT OF CANTHAXANTHIN AND FROMABOUT 25% TO 50% BY WEIGHT OF A CAROTENOID SELECTED FROM THE GROUPCONSISTING OF B-CAROTENE, B-APO-8''CAROTENAL, B-APO-8''-CAROTENIC ACIDETHYL ESTER, BIXIN, ZEAXANTHIN, CROCETIN AND CITRANAXANTHIN, FOR APERIOD OF FROM ABOUT 10 TO ABOUT 20 DAYS PRIOR TO EXPECTED EXPOSURE TOSUNLIGHT.
 2. The method of claim 1 wherein component (b) is a mixturecontaining canthaxanthin and Beta -carotene.
 3. The method of claim 1wherein component (b) is a mixture containing canthaxanthin and Beta-apo-8''-carotenal.
 4. The method of claim 1 wherein component (b) is amixture containing canthaxanthin and Beta -apo-8''-carotenoic acid ethylester.
 5. The method of claim 1 wherein component (b) is a mixturecontaining canthaxanthin and citranaxanthin.